Reduced clot debris size in sonothrombolysis assisted with phase-change nanodroplets

Thrombosis-related diseases such as stroke, deep vein thrombosis, and others represent leading causes of mortality and morbidity around the globe. Current clinical thrombolytic treatments are limited by either slow reperfusion (drugs) or invasiveness (catheters) and carry significant risks of bleeding. High intensity focused ultrasound (HIFU) has been demonstrated to be a non-pharmacological, non-invasive but yet efficient thrombolytic approach. However, clinical concerns still remain related to the clot debris produced via fragmentation of the original clot potentially being too large and hence occluding downstream vessels, causing hazardous emboli. In this study, we introduced phase-change nanodroplets into pulse HIFU-mediated thrombolysis. The size distribution of the clot debris generated in sonothrombolysis with and without nanodroplets was compared. The effects of nanodroplet concentration, acoustic power and pulse repetition frequency on the clot debris size were further evaluated. It was found that the volume percentage of the large clot debris particles (above 10 μm in diameter) was smaller and the average diameter of the clot debris reduced significantly in nanodroplets-assisted sonothrombolysis. The stable cavitation dose was higher in sonothrombolysis without nanodroplets but the inertial cavitation dose showed no significant differences under two conditions. Besides, the average diameter decreased with increasing nanodroplet concentration and acoustic power when calculated by number percentage, but was found to be similar when calculated by volume percentage. In addition, the number percentage of the clot debris above 30 μm was demonstrated to be larger upon applying a higher pulse repetition frequency. Taken in concert, this study demonstrated that the introduction of phase-change nanodroplets could provide a safer sonothrombolysis method by reducing the overall clot debris size.